p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21

Cell. 1994 Jul 15;78(1):67-74. doi: 10.1016/0092-8674(94)90573-8.

Abstract

Using a yeast interaction screen to search for proteins that interact with cyclin D1-Cdk4, we identified a 27 kDa mouse protein related to the p21 cyclin-Cdk inhibitor. p27 interacts strongly with D-type cyclins and Cdk4 in vitro and more weakly with cyclin E and Cdk2. In mouse fibroblasts, p27 is associated predominantly with cyclin D1-Cdk4. Recombinant p27 is a potent inhibitor of cyclin D1-Cdk4 and cyclin A-Cdk2 protein kinase activity and a weaker inhibitor of cyclin B1-Cdc2. Overexpression of p27 in Saos-2 cells causes G1 arrest. p27 protein levels do not change as serum-stimulated quiescent mouse fibroblasts progress through the cell cycle. p27 is identical to p27Kip1, a cyclin-Cdk inhibitor present in TGF beta-treated cells. p27 has the hallmarks of a negative regulator of G1 progression and may mediate TGF beta-induced G1 arrest.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CDC2-CDC28 Kinases*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins*
  • Cell Line
  • Cloning, Molecular
  • Cyclin D1
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases*
  • Cyclins / genetics
  • Cyclins / metabolism*
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Fungal Proteins / pharmacology*
  • G1 Phase / drug effects*
  • Gene Expression Regulation
  • Mice
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / pharmacology*
  • Molecular Sequence Data
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Open Reading Frames
  • Protein Kinase Inhibitors*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins*
  • RNA, Messenger / analysis
  • Recombinant Fusion Proteins / metabolism
  • Sequence Analysis, DNA
  • Tumor Suppressor Proteins*
  • Yeasts / metabolism

Substances

  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Cyclins
  • Fungal Proteins
  • Microtubule-Associated Proteins
  • Oncogene Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cdk2 protein, mouse
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases

Associated data

  • GENBANK/U10440